Zika virus (ZIKV) (Flaviviridae, flavivirus), an emerging mosquito-borne virus, was first detected in Brazil in 2015 and has since spread to at least 38 countries in South America, Central America and Caribbean. The World Health Organization declared the ZIKV pandemic a public health emergency on February 1, 2016. In approximately 20% of infected humans, ZIKV causes a febrile illness that can include rash, arthralgia and conjunctivitis. In addition, ZIKV has been associated with the development of microcephaly and lissencephaly and ocular lesions in infants born to women who acquired ZIKV infection during early pregnancy. In adults, ZIKV has also been associated with Guillan-Barr syndrome and other neurological complications including hearing loss and tinnitus. Very little research has been done with ZIKV and our understanding of the virology, immunology and pathogenesis of ZIKV disease in humans is very limited. There are no established animal models, although a few studies have been imitated in the past few months. (NHP), and until February 2016, no NHP had been inoculated with contemporary pandemic ZIKV isolates. Although ZIKV is a mosquito-transmitted virus, reports of women becoming infected through sexual intercourse with ZIKV infected men have come from countries with no evidence of mosquito transmission. In fact, during February 6?22, 2016, health officials from several states reported two confirmed and four probable cases of ZIKV sexual transmission to CDC. In all cases, condomless vaginal intercourse occurred when the male partner was symptomatic or shortly after symptoms resolved. In addition, there are earlier reports suggesting ZIKV sexual transmission prior to the current outbreak, ZIKV virus has been found in semen and a recent report suggested ZIKV persists in semen for more than 60 days after onset of symptoms. Despite these observations the frequency and efficiency of sexual ZIKV transmission is unclear. To better understand the potential for sexual transmission of ZIKV and to test whether vaccines can prevent ZIKV transmission by this route an animal model is needed. The goal of this R21 is to develop a NHP model of vaginal ZIKV transmission. We will conduct initial studies to determine the efficiency of vaginal ZIKV transmission and characterize the virology of the infection. Further, we will characterize and compare innate and adaptive immune responses to ZIKV in the genital tract and systemic compartment.